1. Field of the Invention
This invention relates to a synthetic peptide of the human malaria Plasmodium vivax, more particularly the invention relates to a synthetic or recombinant peptide containing the sequence AGDR which is a protective epitope found on the circumsporozoite (CS) protein of the sporozoites of the human malaria Plasmodium vivax. When a monoclonal antibody specific for this four amino acid sequence binds to the CS protein of the P. vivax sporozoite in vivo, infection is prevented.
2. Description of the Prior Art
Of the four human malarias, P. vivax and P. falciparum are the most common and cause the majority of the malaria-induced disease seen worldwide. Prevention of infection by these human parasites would alleviate a major health problem in the tropical and subtropical areas of the world. The most promising method for the control of malaria appears to be the development and use of vaccines. One approach to malaria vaccine development involves the use of the CS protein as a vaccine antigen. This protein covers the surface of the sporozoite. The sporozoite is the life stage of the parasite which is transmitted to humans by feeding female Anopheline mosquitoes. Evidence from both mouse and human malarias indicates that antibodies to the CS protein can provide protection in vivo against infection by sporozoites (Charoenvit et al., Infect. Immunity 55: 604, 1987; Charoenvit et al., in press, J. Immun. 1991; Charoenvit et al., in press, Science 1990).
In 1985, McCutchan and colleagues sequenced the gene for the CS protein in P. vivax and determined the amino acid sequence derived from the gene (McCutchan et al., Science 230: 1381, 1985). In 1987, McCutchan and Wistar, in U.S. Pat. No. 4,693,994, described a repeated nine amino acid sequence within the CS protein as an immunodominant synthetic peptide. The repeated sequence is Gly-Asp-Arg-Ala-Asp-Gly-Gln-Pro-Ala. In the '994 patent and in other publications, McCutchan/Wistar maintain that the nine amino acid sequence is capable of inducing antibodies protective against P. vivax malaria. Experimental evidence indicates that while the McCutchan/Wistar sequence stimulates the development of anti-CS antibody in humans, it is not capable of inducing protective antibodies. In an article published in Am. J. Trop. Med. Hyg. 40(5), p 455-464 (1989), Collins et al. describes tests in which Saimiri monkeys (Saimiri sciureus boliviensis), which are susceptible to human vivax malaria, were immunized with two different preparations (VIVAX-1 and NS1.sub.81 V20). Both preparations contain the McCutchan/Wistar peptide (Gly-Asp-Arg-Ala-Asp-Gly-Gln-Pro-Ala). When these monkeys were challenged with 10.sup.4 P. vivax sporozoites, there was no significant protection.
Nussenzweig et al., in U.S. Pat. No. 4,826,957, describes an immunogenic recombinant yeast expression product which contains a long sequence incorporating a portion of the P. vivax circumsporozite. The sequence contains multiple repeats of the sequence Gly-Asp-Arg-Ala-Asp-Gly-Gln-Pro-Ala as part of a complex polypeptide. The vaccine causes the formation of antibodies, to Gly-Asp-Arg-Ala-Asp-Gly-Gln-Pro-Ala, but does not provide consistent protection against challenge with malaria sporozoites. There is a need for a simple material to generate a vaccine against P. vivax.